Mesenchymal stem cells promote human melanocytes proliferation and resistance to apoptosis through PTEN pathway in vitiligo
Mesenchymal stem cells promote human melanocytes proliferation and resistance to apoptosis through PTEN pathway in vitiligo
复制标题
间充质干细胞在白癜风中通过PTEN途径促进人黑素细胞增殖和抗凋亡。
DOI：
10.1186/s13287-019-1543-z
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发表时间：
2020-01-15
影响因子：
7.5
通讯作者：
Wu, Liangcai
中科院分区：
文献类型：
--
作者：
Zhu, Lifei;Lin, Xi;Wu, Liangcai
背景白癜风是一种获得性慢性复发性皮肤病，引起色素脱失，导致黑素细胞(MC)的选择性破坏。然而，导致黑素细胞功能障碍和死亡的机制尚不清楚。方法采用RNA测序、免疫组织化学和免疫印迹等方法，研究白癜风患者皮损中磷酸酶和张力蛋白同源蛋白(PTEN)/磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(AKT)通路的激活模式。我们还在Transwell系统中将原代黑素细胞与间充质干细胞(MSCs)共培养，以探讨MSCs如何抑制黑素细胞中的PTEN/PI3K/AKT通路。结果白癜风正常皮肤-皮损交界处皮肤呈现PTEN的高表达，导致S-473AKT磷酸化受抑。此外，PTEN过表达导致了氧化应激诱导的黑素细胞的凋亡。与MSCs共培养可促进人黑素细胞增殖，抑制PTEN的表达，从而抑制氧化应激诱导的细胞凋亡。结论白癜风患者存在PTEN的高表达，可能在黑素细胞损伤中起一定作用。此外，我们的研究为MSCs靶向PTEN/PI3K/AKT通路调控人黑素细胞的增殖和凋亡提供了证据，表明MSCs可能成为白癜风的一种有前途的治疗方法。
Background Vitiligo is an acquired chronic and recurrent skin disease that causes a depigmentation disorder, resulting in selective destruction of melanocytes (MC). However, the mechanism that leads to melanocyte dysfunction and death remains unclear. Methods We performed RNA sequencing, immunohistochemistry, and immunoblotting to characterize the patterns of phosphatase and tensin homolog (PTEN)/phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) pathway activation in vitiligo. We also cocultured primary melanocytes with mesenchymal stem cells (MSCs) in a Transwell system to explore how MSCs inhibit the PTEN/PI3K/AKT pathway in melanocytes. Results We identified that vitiligo normal-lesional junction skin presented with high expression of PTEN, which led to the inhibition of AKT phosphorylation (p-AKT) at S-473. Furthermore, PTEN overexpression led to oxidative stress-induced apoptosis in melanocytes. Coculturing with MSCs enhanced the cell proliferation of human melanocytes and repressed PTEN expression, which inhibited oxidative stress-induced apoptosis. Conclusion We report that vitiligo patients present with high PTEN expression, which may play a role in the impairment of melanocytes. Furthermore, our study provides evidence that MSCs target the PTEN/PI3K/AKT pathway to regulate cell proliferation and apoptosis in human melanocytes, indicating that MSCs may serve as a promising therapy for vitiligo.